175. Delivery Via Non-Viral Options to the Auditory Structures

Nearly 50 million people in the US alone are affected by disorders of the inner ear making hearing loss one of the mose common neurodegenerative disorders. Recent studies have demonstrated a number of potential applications for gene therapy in the inner ear including regeneration of sensory cells.Most studies of gene transfer to the inner ear have used viral vectors. The flexibility and non toxic properties of non viral gene delivery systems may be ideal for the inner ear which is easily damaged by inflammation that may be associated with some viral vectors.We compared three types of delivery vehicles including cationic polyamines, dendrimers and liposomes carrying a GFP expressing plasmid driven by a hCMV promoter. Two separate delivery routes to the inner ear were used: Vectors were delivered via application to the round window or delivery into the cochlea via a fenestration of the utricle. We analyzed the distribution of GFP with the inner ear after delivery of varying concentrations of vector and plasmid.All vectors used delivered to the spiral ganglion cells. Delivery to hair cells was seen using cationic polyamine vectors. Overall these vectors appeared to deliver more efficiently, to the basal turn of the cochlea, suggesting that distribution within the fluid filled cochlea may be constrained by diffusion.Non viral gene transfer using advanced non viral vectors may provide a delivery system to the sensory hair cells and spiral ganglion cells. Options to modify viral vector systems for enhanced targeting may still provide better transfection rates.